More specifically, the invention relates a liposome-encapsulated ciprofloxacin, and to the use of such composition for stimulate host cell-mediated immunity to resist microbial infections and to enhance macrophage killing of microbial pathogens and cancer cells.
The present inventor has already proposed use of liposome-encapsulated ciprofloxacin as an antibiotic (see Canadian Patent Application Serial No. 2,101,241, filed Jul. 23, 1993). Further research by the inventor has a liposome-encapsulated quinolone, specifically ciprofloxacin can be used as an immunoprophylactic and immunotherapeutic agent.
Chronic bacterial, viral and fungal infections, as well as a number of neoplastic diseases can cause significant impairment to a host's immune defense system ability to fight diseases (D. A. Cooper et at, "Characterization of T lymphocyte responses during primary infection with human immunodeficiency virus", 1988, J. Infect. Dis. 157:889-896" and A. Sher et al, "Role of T-cell derived cytokines in the downregulaton of immune responses in parasitic and retroviral infection", 1992, Immunol. Rev. 127:183-204). In cancer patients undergoing chemo-and/or radiation therapy, the immune system is usually further suppressed, rendering them susceptible to infections. Some antibiotics currently used to prevent infections in immuno comprised individuals are themselves known to cause further suppression of the cellular and humoral immune responses (L. Bassie et al, "Conditions for immunosuppression by rafampicin", 1993, J. Infect. Dis. 128:736-744, T. E. Miller et al, "Clinical infections, antibiotics and immunosuppression: A puzzling relationship", 1981, The Amer. J. Med. 71:334-336 and W. E. Hauser et al, "Effect of antibiotics on the immune response", 1982, The Amer. J. Med. 72:711-716).
Attempts to elevate the host immune defense using immunotherapy with agents such as exogenous cytokines have become increasingly important in clinical applications in recent years, particularly for the immune therapy of AIDS, other immune deficiency disorders and cancer. However, such exogenous cytokines, including interleukins, interferons and tumor necrosis factors are known to cause serious toxic side effects (J. R. Quesada et al, "Clinical toxicity of interferons in cancer patients: a review", 1986, J. Clin. Oncol. 4:234-243 and C. A. Dinarello, "Role of interleukin-1 in infectious diseases", 1992, Immunol. Rev. 127:119-146). Moreover, the cytokines are expensive, and are rapidly cleared from the general circulation following systemic administration (B. A. Beutler et al, "Cachectin/tumor necrosis factors: production, distribution, and metabolic fate in vivo", 1985, J. Immunol. 135:3972-3977).